The role of cGAS-STING pathway in the development of radiation-induced lung injury.

BACKGROUND AND PURPOSE: Radiation-induced lung injury (RILI) limits the efficacy of thoracic radiotherapy. However, the underlying mechanism of RILI remains unclear. cGAS-STING pathway is reported to be involved in the recognization of cytosolic dsDNA and various inflammatory diseases. This study aimed to investigate the role of cGAS-STING pathway in the development of RILI.

MATERIALS AND

METHODS

A pre-clinical mouse model of RILI was established by whole thorax irradiation and confirmed using H&E and Masson's trichrome staining. STING agonist (DMXAA) and antagonist(C-176) were administrated to modulate cGAS-STING pathway in vivo. Western blot and ELISA were used to determine the expression levels of different proteins.

RESULTS

Quantitation analysis showed dsDNA accumulation in lung tissue and western blot showed the up-regulation of cGAS and STING protein level post-irradiation, indicating pathway activation. Histological evaluation showed that C-176 administration ameliorated radiation-induced pulmonary inflammation and fibrosis, while DMXAA exhibited contrary effects. In further in vitro study, the release of dsDNA induced by radiation led to the activation of cGAS-STING pathway in RAW 264.7 cells, resulting in the polarization into M1 phenotype and pro-inflammatory production.

CONCLUSION

In summary, our data demonstrated a link between cGAS-STING pathway and the development of RILI, indicating its potential application in clinic.